Received: 18 July 2019 | Accepted: 15 August 2019

DOI: 10.1002/brb3.1408

REVIEW

The role of the brain–gut–microbiota axis in psychology: The

importance of considering gut microbiota in the development,
perpetuation, and treatment of psychological disorders

Michael Ganci1 | Emra Suleyman1 | Henry Butt2,3 | Michelle Ball1

1
Psychology Department, Institute for
Health and Sport, Victoria University, Abstract
Melbourne, Vic., Australia Introduction: The prevalence of psychological disorders remains stable despite
2
Bioscreen Yarraville (Aust) Pty Ltd,
steady increases in pharmacological treatments suggesting the need for auxiliary
Melbourne, Vic., Australia
3
Melbourne University, Melbourne, Vic.,
treatment options. Consideration of the brain–gut–microbiota axis (BGMA) has made
Australia inroads into reconceptualizing psychological illness from a more holistic perspective.

Correspondence
While our understanding of the precise role of gut microbiota (GM) in psychological
Michael Ganci, Psychology Department, illness is in its infancy, it represents an attractive target for novel interventions.
Institute for Health and Sport, Victoria
University, Melbourne, PO Box 14428,
Method: An extensive review of relevant literature was undertaken.
Melbourne, Vic. 8001, Australia. Results: Gut microbiota are proposed to directly and indirectly influence mood, cog‐
Email: Michael.ganci1@live.vu.edu.au
nition, and behavior which are key components of mental health. This paper outlines
Funding information
how GM may be implicated in psychological disorders from etiology through to treat‐
This paper did not receive any specific
grant from funding agencies in the public, ment and prevention using the Four P model of case formulation.
commercial, or not‐for‐profit sectors.
Conclusion: Moving forward, integration of GM into the conceptualization and treat‐
However, the first author was supported
by a postgraduate scholarship with no ment of psychological illness will require the discipline of psychology to undergo a
restrictions on publications cofunded by
significant paradigm shift. While the importance of the GM in psychological well‐
Bioscreen, an industry partner of Victoria
University. being must be respected, it is not proposed to be a panacea, but instead, an additional
arm to a multidisciplinary approach to treatment and prevention.

KEYWORDS
allostatic load, gut microbiota, precipitating factors, predisposing factors, protective factors,
psychology

1 | I NTRO D U C TI O N to the intertwined coevolution between humans and our resident

Burgeoning research regarding the role of the gut and its microbial
inhabitants in the pathophysiology of psychological illness is gain‐
ing momentum. Early evidence points to gut microbiota (GM) as a
possible missing link in the conceptualization and treatment of psy‐
chological illness that sees disparities between conventional treat‐
ment methods and prevalence rates. When discussing the role of
GM in behavior, health, and disease, it is important to pay respect
microbes. It is suggested that the sharp increase in various disease
states over the last 50–100 years (Campell, 2014; Linneberg et al.,
2000) can be, at least in part, explained by relatively recent dietary
and lifestyle changes in the context of human evolution (Broussard
& Devkota, 2016). Currently, humans, particularly those in indus‐
trialized countries, are living in an environment to which they have
not adaptively evolved (Gluckman, Low, Buklijas, Hanson, & Beedle,
2011). An unintended consequence of industrialization, these

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© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Brain and Behavior. 2019;9:e01408.  wileyonlinelibrary.com/journal/brb3 | 1 of 19

https://doi.org/10.1002/brb3.1408
2 of 19 | GANCI et al.
changes are putting the GM under evolutionary pressure to shift
from a previously mutualistic relationship with their human host to
a more antagonistic one (Broussard & Devkota, 2016; Quercia et al.,
2014). This is due to human evolution requiring significantly more
time (Uyeda, Hansen, Arnold, & Pienaar, 2011) compared to single‐
celled organisms such as GM that evolve and adapt to environmental
and internal states much more rapidly (within as little as 24 hr; David
et al., 2014; Wu et al., 2011). These variations in the evolutionary
pressures and capabilities of the two components (host and GM) of a
single ecosystem (the holobiont; Theis et al., 2016) result in systemic
disharmony.
This systemic disharmony leads to symptomatology and disease
states that are the primary target for intervention in current medi‐
cal models, which precludes effective etiology‐focused prevention
(Marvasti & Stafford, 2012). This is exacerbated given that current
medical models are heavily skewed toward treatment over preven‐
tion (Singh, 2010). While there is disagreement over whether the
occurrence of common mental disorders are increasing or whether
their prevalence remains consistent (Friedrich, 2017; Harvey et al.,
2017), the consumption of antidepressant drugs doubled in most, if
not all, Organisation for Economic Co‐operation and Development
(OECD) countries between 2000 and 2015 (OECD, 2017). Despite
this, depression has recently taken over as the leading cause of dis‐
ability worldwide with anxiety also in the top 10 leading causes of
disability (World Health Organisation (WHO) 2017). Furthermore,
subclinical psychological symptoms that do not meet the full
Diagnostic and Statistical Manual for Mental Disorders (DSM) or
International Classification of Diseases (ICD) diagnostic criteria are
also prevalent (Angst, Merikangas, & Preisig, 1997; Haller, Cramer,
Lauche, Gass, & Dobos, 2014; Mathieson, Collings, & Dowell, 2009).
These subclinical symptoms lead to impairment in psychosocial and
work functioning, are a major determinant of sick leave, contribute
to the use of psychotropic drugs and primary health care services,
and reduce quality of life (Haller et al., 2014; Johansen & Dittrich,
2013; Mendlowicz & Stein, 2000).
The conceptualization of the human body as being made up of
separate and distinguishable systems is likely to have contributed
to our current poor appreciation of the complexity of mechanisms
that underlie the etiology and progression of disease. Psychology,
just like many other healthcare professions and medical science dis‐
ciplines, specialize and focus on specific body systems. For example,
treatment of psychological symptoms and disorders tends to be cen‐
tral nervous system (CNS)‐centric with the brain being the principle
target for both psychotherapy and psychopharmacology while pe‐
ripheral systems, such as the gut, receive little attention. While there
is no doubt that specialization has its benefits and has contributed
to the progression of medical knowledge, it also has its drawbacks.
Operating within these constrictive distinctions imposed by disci‐
plinary specialization means that the complex interplay between
various body systems essential to proper functioning is overlooked.
The true etiology of disease is likely to come from dysregulations in
this interplay which may also go some way to explaining high lev‐
els of comorbidity, particularly between functional gastrointestinal
disorders such as IBS and psychological conditions (Garakani et al.,
2003; Lee et al., 2015).
Within the field of psychology, an integral part of intervention is
case formulation. Essentially, case formulation involves the synthe‐
sis of information about a patient (typically gained through clinical
interviews and formalized cognitive testing) in a meaningful way to
facilitate the development of a treatment plan. A commonly used
model in structuring a case formulation is that of the Four Ps which
represent the predisposing, precipitating, perpetuating, and pro‐
tective factors related to a client's presenting problem and thus the
targets of psychological intervention. As information is drawn from
clinical interviews and cognitive testing, the functioning of a client's
gut is seldom considered in their formulation; thus, important diag‐
nostic and treatment options may be missed. It is the contention of
this paper to demonstrate that GM are intimately linked with each of
these four pillars of psychological intervention and thus each stage
of disease, from etiology through to treatment and prevention. This
paper adds to the burgeoning research into the brain–gut–microbi‐
ota axis (BGMA; Kelly, Clarke, Cryan, & Dinan, 2016) demonstrat‐
ing that the discipline of psychology is on the cusp of a significant
paradigm shift, moving away from CNS‐centric approaches toward
a more holistic conceptualization of health and disease which inte‐
grates other body systems. We echo the sentiment of Allen, Dinan,
Clarke, and Cryan (2017) who call for a challenge to the reductionist
approaches in psychology in favor of a multidisciplinary approach to
conceptualizing and treating psychological disorders. In taking the
unique approach of the Four P model of case formulation, this paper
intends to review existing research on associations between GM and
psychological outcomes, compiling it in a way that is more accessible
to psychologists, especially those who have little previous knowl‐
edge regarding the BGMA.
1.1 | The brain–gut–microbiota axis
The BGMA is increasingly being recognized as playing an important
role in homeostasis and consequentially, health and disease states
(e.g., Mu, Yang, & Zhu, 2016; Rea, Dinan, & Cryan, 2016). The BGMA
refers to the relationship between the brain and the gut while ac‐
knowledging the important moderating role of GM (e.g., Carabotti,
Scirocco, Maselli, & Severi, 2015; Grenham, Clarke, Cryan, & Dinan,
2011). Largely recognized as a bidirectional relationship (e.g., Rhee,
Pothoulakis, & Mayer, 2009), research continues to uncover the true
complexities of this communication network which Rea et al. (2016)
more accurately define as a multidirectional relationship. It is multi‐
directional in the sense that each component of this extensive com‐
munication network has the ability to moderate and manipulate the
function of the other systems involved. Communication between
the brain and the gut is maintained via a complex network including
the CNS, autonomic nervous system (ANS), enteric nervous system
(ENS), hypothalamic–pituitary–adrenal (HPA) axis, neural, endocrine
and immune systems (e.g., Carabotti et al., 2015; Cryan & Dinan,
2012; Mayer, 2011; Moloney, Desbonnet, Clarke, Dinan, & Cryan,
2014). Essentially, the BGMA provides a network for signals from
GANCI et al.
the brain to influence the motor, sensory, and secretory functions
of the gut while simultaneously allowing signals and metabolites
from the GM to influence brain development, biochemistry, func‐
tion, and behavior (e.g., Cryan & O'Mahony, 2011; Grenham et al.,
2011; Marques et al., 2014). This communication system presents an
exciting and novel target for psychological intervention, providing a
deeper understanding of the biological underpinnings of psychologi‐
cal illnesses. It is hoped that developing a greater understanding of
the BGMA as it relates to the Four Ps of case formulation will provide
psychologists with an additional tool in the treatment of their clients.
1.2 | Is diet the chicken, or the egg?
The relationship between diet and GM is an intriguing one, ironically
reminiscent of the idiom regarding which came first, the chicken or
the egg. Once thought to be unidirectional (diet influencing the com‐
position of the microbiota), recent evidence suggests the relation‐
ship could in fact be bidirectional, with microbes also being able to
influence food choice and dietary‐related behaviors (Alcock, Maley,
& Aktipis, 2014).
Diet is arguably one of the most important environmental fac‐
tors in shaping the composition and metabolic activities of GM (De
Filippo et al., 2017; Garcia‐Mantrana, Selma‐Royo, Alcantara, &
Collado, 2018; Voreades, Kozil, & Weir, 2014). As such, diet must
be taken into consideration when discussing potential interventions
involving GM. An extensive review of the relationship between diet
and GM is beyond the scope of this paper, but can be found else‐
where (e.g., Sheflin, Melby, Carbonero, & Weir, 2017; Singh et al.,
2017; Wu et al., 2011). Here, diet is discussed insofar as to high‐
light to psychologists the importance of this environmental factor
in the formulation and treatment of their client's presenting prob‐
lem. While it is not being suggested that psychologists become well
versed in dietetics, gathering general information on a client's diet
may provide further insight into the development and perpetuation
of their presenting problem, and presents as an additional arm to a
multidisciplinary and holistic treatment approach.
Both the content and diversity of an individual's diet are be‐
lieved to be important in maintaining a well‐balanced GM (Heiman &
Greenway, 2016; Oriach, Robertson, Stanton, Cryan, & Dinan, 2016).
Diet quality has also been highlighted as a potential risk or protective
factor for conditions such as depression (Jacka et al., 2017; Koopman
& El Aidy, 2017; Lai et al., 2014). In regards to dietary content, the
industrial revolution saw a significant increase in highly processed
cereals rich in carbohydrates, refined sugars, sodium, omega‐6, and
trans‐fatty acids. Concurrently, potassium, complex carbohydrates,
fiber, omega‐3, and unsaturated fatty acids were considerably re‐
duced (Rubio‐Ruiz, Peredo‐Escárcega, Cano‐Martínez, & Guarner‐
Lans, 2015). These changes are reflective of what is today termed
the “Western‐style diet,” one that has been shown to impair immune
function and promote inflammation (Myles, 2014). This is concerning
given that inflammation is believed to underlie and perpetuate many,
if not all, psychological and neurodegenerative illnesses (Almond,
2013; Miller & Raison, 2016; Rea et al., 2016). Worryingly, dietary
| 3 of 19
diversity has been further reduced over the past 50 years with an
ever increasing preference for convenience and taste (Glanz, Basil,
Maibach, Goldberg, & Snyder, 1998; Heiman & Greenway, 2016;
Poti, Mendez, Ng, & Popkin, 2015). Essentially, this means that
current human diets are not providing GM with the resources they
require to perform their myriad of complex tasks involved in host
homeostasis and consequently health and disease. Adding support
to this contention, Jacka et al. (2017) conducted a clinical trial which
demonstrated that adherence to a modified Mediterranean diet
resulted in significantly greater improvement in depression ratings
from baseline compared to a social support control group.
While diet is one way through which a host can modulate their
GM, microbes are themselves able to influence eating behaviors of
their host (Alcock et al., 2014). Microbes in the gut must cooper‐
ate and share limited resources (space and nutrients) to promote
stable coexistence and ecological diversity (Allen & Nowak, 2013).
This means that these microorganisms are under selective pres‐
sure to ensure their own survival and must therefore compete for
available resources (Hibbing, Fuqua, Parsek, & Peterson, 2010). As
such, microbes are proposed to manipulate the eating behavior of
the host by either generating cravings for foods that they thrive on
or those which suppress their competitors, or by influencing mood
which leads to the intake of foods that enhance that species' fitness
(Alcock et al., 2014; Leitao‐Goncalves et al., 2017).
1.2.1 | Dietary‐derived short‐chain fatty acids
A continued loss of fiber from the Western diet will inevitably lead
to continued depletion of short‐chain fatty acids (SCFAs; Broussard
& Devkota, 2016) with downstream effects on the development and
perpetuation of psychological illnesses through their immunoregula‐
tory effects (Rogers et al., 2016). SCFAs (acetic, butyric, and pro‐
pionic acids in particular) are one of the main metabolites of GM
(Carabotti et al., 2015; Smith et al., 2013). They are the end products
of dietary fiber fermentation and have been shown to have many
beneficial effects on host health (Bourassa, Alim, Bultman, & Ratan,
2016; den Besten et al., 2013).
In the brain, SCFAs demonstrate neuroprotective properties
(Sun et al., 2015) with butyrate in particular having a protective ef‐
fect on psychological and neurodegenerative disorders (Bourassa
et al., 2016). Peripherally, SCFAs are believed to influence the
size and function of regulatory T cells which play a crucial role
in regulating inflammation and immune homeostasis (Hakansson
& Molin, 2011; Smith et al., 2013). Additionally, SCFAs (together
with enzymes also produced by the GM) enhance intestinal bar‐
rier functioning through their regulation of tight junction (TJ) pro‐
teins (e.g., Anderson et al., 2010; Bischoff et al., 2014; Peng, Li,
Green, Holzman, & Lin, 2009). Abnormal intestinal permeability
(leaky gut) results in increased translocation of toxins and GM
across the epithelial barrier which consequently trigger an inflam‐
matory immune response that can dysregulate ENS and systemic
immune functioning (Berkes, Viswanathan, Savkovic, & Hecht,
2003; Carabotti et al., 2015; Fasano, 2012; Smith et al., 2013).
4 of 19 | GANCI et al.
This immune response is believed to be the instigator of resultant
symptom expression including psychological disorders such as de‐
pression (e.g., Maes et al., 2013; Mulak & Bonaz, 2015; Sheedy et
al., 2009).
Also via their influence on TJ proteins, SCFAs are believed to reg‐
ulate the permeability of the blood–brain barrier (BBB; Braniste et
al., 2014). Dysregulation of the BBB has been associated with neu‐
ropsychological conditions including Alzheimer's disease (Kuhnke
et al., 2007) and autism (Fiorentino et al., 2016). Schoknecht and
Shalev (2012) suggest that depression and schizophrenia may also
be related to BBB dysfunction. Although further research is needed,
these associations are highly plausible given the BBB is responsi‐
ble for regulating access of circulating macromolecules and poten‐
tial neurotoxins to the brain (Fiorentino et al., 2016; Patel & Frey,
2015). As evidence of microbial involvement, Braniste et al. (2014)
found that germ‐free (GF) mice (those devoid of bacterial coloni‐
zation and therefore lacking conventional gut flora) have increased
BBB permeability compared to specific pathogen‐free (SPF) mice
that have conventional GM colonization free of any known patho‐
gens. Colonization of GF mice with known SCFA‐producing bacterial
strains (Clostridium tyrobutyricum and Bacteroides thetaiotaomicron)
was found to normalize BBB function (Braniste et al., 2014). There
is also evidence to suggest that SCFAs are involved in glucose me‐
tabolism, reducing adiposity, appetite regulation, and energy ho‐
meostasis (Byrne, Chambers, Morrison, & Frost, 2015; Chambers et
al., 2015; Kondo, Kishi, Fushimi, Ugajin, & Kaga, 2009; Morrison &
Preston, 2016).
1.3 | Behavior
Studies using GF mice have provided the greatest depth of infor‐
mation regarding the influence of GM on host behavior. Such pre‐
clinical work gives useful insights into the physiological mechanisms
through which the BGMA functions. For example, GF mice dem‐
onstrate altered expression of brain‐derived neurotrophic factor
(BDNF) and SCFA while also exhibiting altered HPA axis functioning,
anxious and depressive behaviors, and social functioning (Arentsen,
Raith, Qian, Forssberg, & Diaz Heijtz, 2015; Luczynski et al., 2016;
Neufeld, Kang, Bienenstock, & Foster, 2011; Sudo et al., 2004).
In both animal and human models, manipulation of GM has also
been demonstrated to alter levels of stress hormones corticotro‐
pin‐releasing factor (CRF) and cortisol (Yarandi, Peterson, Treisman,
Moran, & Pasricha, 2016). Many of these abnormalities have been
shown to be rectified by colonization with the feces from SPF mice
or with specific probiotics (e.g., Bercik et al., 2011; Desbonnet et al.,
2010; Sudo et al., 2004). However, Bravo et al. (2011) found that
ingestion of probiotics was only beneficial in mice which had an in‐
tact vagus nerve, demonstrating the importance of the vagal path‐
way in brain–gut communication. Additionally, Sudo et al. (2004)
demonstrated that recolonization was only effective if it occurred
within a critical period, providing evidence for a fundamental role
of GM in the development of crucial systems involved in behavioral
outcomes.
A recently proposed way in which GM may manipulate host
behavior is via their relationship with personality traits. Kim et al.
(2018) found an increased abundance of Gammaproteobacteria in
those with high neuroticism, as well as those with low extraversion.
Low conscientiousness was associated with an increased abundance
of Proteobacteria and a decreased abundance of Lachnospiraceae
while those with high levels of openness demonstrated greater phy‐
logenic diversity and richness (Kim et al., 2018). As this was the first
study to have investigated the link between GM and personality di‐
rectly, further research is required to elucidate these relationships.
The relationship between personality and GM presents as an intrigu‐
ing area of exploration, given that personality traits have a strong
association with behavioral patterns in addition to physiological
and psychological health outcomes (e.g., Ferguson, 2013; Kim et al.,
2018; Srivastava & Das, 2015).
Additional evidence linking GM composition and behavior comes
from the study of patients following gastric bypass surgery. Behavioral
changes following gastric bypass surgery include patients feeling less
hungry and having a preference for healthier foods (Behary & Miras,
2015) which is likely related to changes in neural responses to food
(particularly high‐calorie foods) in key areas of the mesolimbic re‐
ward pathway (Ochner et al., 2011, 2012). It is tempting to speculate
that these changes are associated with the compositional changes
in GM following gastric bypass surgery (Furet et al., 2010; Liou et
al., 2013; Zhang et al., 2009). Additionally, improvements in qual‐
ity of life and levels of depression have been shown to persist two
years after surgery (Karlsson, Sjostrom, & Sullivan, 1998; Mokhber,
Shaghayegh, Talebi, & Tavassoli, 2016). These improvements may be
the result of reduced adipose tissue which has downstream effects
on GM and their role in inflammation and other related functions.
While causational evidence is currently unavailable, correlational re‐
search linking GM and mood (Jiang et al., 2015) suggest that changes
in GM composition following gastric bypass surgery may also have a
direct influence on mood. Improvements in mood may consequently
encourage healthier food choices and eating behaviors (Christensen
& Brooks, 2006), exemplifying the potential for a cyclical relationship
involving diet, GM, and mood that is beneficial to overall health.
Given the possible role of GM in eating behaviors, and their
ability to influence hunger and satiety (Cani et al., 2009) and neuro‐
peptide and endocrine regulation (Holzer & Farzi, 2014), a relatively
new line of inquiry has emerged investigating GM involvement in
eating disorders which are traditionally recognized as psychological
disorders (Kleiman et al., 2015; Lam, Maguire, Palacios, & Caterson,
2017). Associations between GM composition and eating disorder
psychopathology were also found by Kleiman et al. (2015), further
suggesting that the GM play a role in the psychology of food choice
and eating behaviors. Given that diet is a key determinant of GM
composition and that eating disorders are categorized by extreme
dietary changes, the GM present as a logical target for inclusion in
multifaceted intervention.
While this paper focuses mainly on unconscious mechanisms un‐
derlying the relationship between GM and psychological outcomes
(such as interoceptive processes and neurotransmitter production), it
GANCI et al. | 5 of 19

Endocrinological Neuronal Immunological

Neurotransmi er
produ on Altered func on
HPA axis Inflamma on
(Allosta response) (Allosta response)
Blood brain
barrier

Homeosta
emo ons Allosta c
overload

Microbial Altered
Interoc on Leaky gut
SCFA
dysbiosis
produ on

Symptom
expression

F I G U R E 1 Factors influencing the multidirectional communication between the brain and the gut. Double‐headed arrows demonstrate
a bidirectional relationship, with broken arrows demonstrating proposed but not yet established relationships. The figure demonstrates
the three main well‐established pathways of communication between the brain and the gut, being endocrinological, neuronal, and
immunological. The figure also illustrates the bidirectional relationships between microbial dysbiosis and the HPA axis, neurotransmitter
production, the function of the blood–brain barrier, and inflammation which are believed to alter their functioning as an allostatic response
to homeostatic emotions. It is proposed that microbial dysbiosis itself is able to be detected via the interoceptive system which then triggers
these homeostatic emotions

is acknowledged that conscious mechanisms also have potential psy‐
chological implications. For example, gastrointestinal symptoms can
be noticeably unpleasant and, particularly in IBS sufferers, can lead to
impairment in daily functioning (Ballou, Bedell, & Keefer, 2015), anxi‐
ety and depression (Roohafza et al., 2016), avoidance behaviors (Van
Oudenhove et al., 2016), and poor quality of life (Canavan, West, &
Card, 2015). Conscious mechanisms can also lead to positive psycho‐
logical outcomes as exemplified by patients following gastric bypass
surgery. For example, noticeable changes in body composition can
result in more positive body image which in itself is related to psycho‐
logical well‐being, particularly after body contouring surgery (Jumbe,
Hamlet, & Meyrick, 2017; Sarwer & Steffen, 2015; Song et al., 2016).
These changes can then encourage long‐term weight loss maintenance
behavior (Palmeira et al., 2010).
1.4 | Neurotransmitters
Perhaps the most obvious association between GM and psychologi‐
cal illnesses is the ability of GM to manipulate the production and
action of several key neurotransmitters (e.g., Anderson & Maes,
2015; Lyte, 2011; O'Mahony, Clarke, Borre, Dinan, & Cryan, 2015).
GM regulate the metabolism and concentration of amino acids which
serve as precursors for several neurotransmitters including gamma‐
aminobutyric acid (GABA), serotonin, melatonin, and dopamine,
among others (Clarke et al., 2014; Evrensel & Ceylan, 2015; Jenkins,
Nguyen, Polglaze, & Bertrand, 2016; Zagajewski et al., 2012). As
such, it is highly plausible that GM are able to influence brain chemis‐
try, which consequentially regulates cognition, mood, and behavior.
As depicted in Figure 1, demonstrating bidirectionality, GM can also
be directly affected by neurochemicals which alter bacterial growth
and pathogenicity (Lyte, 2011). Table 1 displays some of the key neu‐
rotransmitters synthesized by GM whose dysregulation is associated
with psychological disorders. While neurotransmitters produced in
the gut may not directly influence brain chemistry as they do not
pass through the BBB, they are able to influence the CNS through
mechanisms including direct stimulation of the vagus nerve, as well
as using indirect circulatory and immune pathways (Sampson &
Mazmanian, 2015). For example, tryptophan, the precursor molecule
 6 of 19

TA B L E 1 Gut bacteria associated with the synthesis of key neurotransmitters

|

Neurotransmitter Psychiatric conditions related

Genus/species (precursor) CNS effect Peripheral effect to dysregulation References

Candida; Streptococcus;
Escherichia; Enterococcus;
Lactobacillus bulgaricus
Corynebacterium glu‐
tamicum; Lactobacillus
plantarum; Lactobacillus
paracasei; Lactobacillus lactis;
Brevibacterium lactofermentum;
Brevibacterium flavum
Lactobacillus; Bifidobacterium;
Escherichia coli; Pseudomonas
Bacillus, Serratia, E. coli
Bacillus; E. coli; Saccharomyces
(dependent on tryptophan
production and serotonin
synthesis)
Serotonin Motor control, cerebellar
(tryptophan) regulation, synaptogen‐
esis, addiction, emotion,
memory, stress
l‐glutamate Excitatory, brain develop‐
ment, synaptic plasticity
GABA Inhibitory, anxiolytic
(l‐glutamate)
Dopamine (l‐Dopa) Reward‐motivated behavior,
motor behavior, cognition,
emotion
Norepinephrine Stress hormone, attentive‐
(dopamine) ness, emotion, sleep,
learning
Melatonin Circadian rhythm, mood
(serotonin)
Circadian rhythm, gut motility,
body temperature, visceral
pain, appetite, modulation of
immune response
Myorelaxant, moderates intes‐
tinal motility, gastric empty‐
ing, gastric acid secretion, and
inhibits GI carcinogens and
tumor growth
Stimulates exocrine secre‐
tion, inhibits gut motility, and
modulates sodium absorption
and mucosal blood flow
Mediates growth and virulence
of potentially pathogenic
bacteria
Gastrointestinal function, pro‐
tects against gut permeability,
anti‐inflammatory, antioxi‐
dant, analgesic
Depression, IBS, autism,
Down's syndrome
Generalized anxiety disorder,
depression, bipolar, schizo‐
phrenia, neurodegeneration
Schizophrenia, Parkinson's
disease, depression, anxiety,
addiction
Depression, schizophrenia
IBS, multiple sclerosis, autism,
Alzheimer's, mood disorders
Arreola et al., (2015), Gulesserian,
Engidawork, Cairns, and Lubec (2000),
Halford and Blundell, (2000), Hood
et al. (2006), Jenkins et al. (2016),
Leonard, (2010), Mazzoli and Pessione
(2016), Marks et al. (2009), Meneses
and Liy‐Salmeron (2012), Müller and
Homberg (2015), Rogers et al. (2016),
Stasi, Rosselli, Zignego, Laffi, and Milani
(2014), Warren and Singh, (1996),
Whitaker‐Azmitia (2001)
Abdou et al. (2006), Boonstra et al.
(2015), Cherlyn et al. (2010), Femenía,
Gómez‐Galán, Lindskog, and Magara
(2012), Hyland and Cryan (2010),
Meldrum (2000), Yoto et al. (2012)
Di Chiara and Bassareo (2007),
Eisenhofer et al. (1997), Freestone
(2013), Grace (2016), Lyte (2011), Meyer
and Feldon (2009), Scheperjans et al.
(2015), Shishov, Kirovskaya, Kudrin, and
Oleskin (2009)
Freestone (2013), Moret and Briley
(2011), Yamamoto and Hornykiewicz
(2004)
Fornaro, Prestia, Colicchio, and Perugi
(2010), Ghorbani, Salari, Shaygannejad,
and Norouzi (2013), Ortiz, Benítez‐King,
Rosales‐Corral, Pacheco‐Moisés, and
Velázquez‐Brizuela (2008), Veatch,
Goldman, Adkins, and Malow (2015),
Wong, Yang, Song, Wong, and Ho (2015)
GANCI et al.
GANCI et al.
to serotonin (which is itself the precursor to melatonin), is able to
pass through the BBB and as such it is likely that metabolites of GM
directly influence brain chemistry (Sampson & Mazmanian, 2015).
1.5 | Interoception and allostatic responses
It is currently unknown whether the interoceptive system is able
to detect microbial dysbiosis (imbalances resulting from the under‐
or overabundance of certain microbial species; DeGruttola, Low,
Mizoguchi, & Mizoguchi, 2016), but considering that gut microbes
are an essential part of human physiology which moderate sev‐
eral homeostatic emotions (Craig, 2002; Mayer, Naliboff, & Craig,
2006; Noakes, 2012; Paulus & Stein, 2010) it is a strong possibility.
Homeostatic emotions are background emotions that may or may
not enter conscious awareness but influence an individual's energy
levels, mood, and disposition (Mayer et al., 2006). Signals from in‐
ternal organs, particularly the gut, continuously communicate with
various regions of the brain including the limbic system, autonomic
and neuroendocrine centers in the hypothalamus, brainstem, and
cortex (Craig, 2002; Holzer & Farzi, 2014; Mayer & Tillisch, 2011).
It is plausible that through the process of interoception, GM are
able to influence human cognition, emotion, and mood through
their involvement in systemic functioning through their various me‐
tabolites (Holzer, 2017; Paulus & Stein, 2010). As such, increasing
rates of disease might be explained by the allostatic load hypoth‐
esis (McEwen, 1998). The allostatic load hypothesis proposes that
rather than having a stable set point, body systems have a range
of set points allowing them to actively adapt to environmental and
internal states. Allostatic load is a term used to refer to the cumu‐
lative cost of allostasis to the body (“wear and tear”; McEwen &
Wingfield, 2003). While adaptive in the short term, allostasis can
become maladaptive, leading to disease, when allostatic measures
are required to vary widely and frequently, or are at extreme val‐
ues for long periods of time (James, 2013). Additionally, allostatic
systems can become dysfunctional when they lose their ability to
change or regulate change (James, 2013). The result of either of
these scenarios is allostatic overload which can lead to symptom
expression, as depicted in Figure 1 (Berger, Juster, & Sarnyai, 2015;
McEwen, 2005; McEwen & Wingfield, 2003). The fact that research
has failed to define the precise composition of a healthy GM due
to immense interindividual differences (Lloyd‐Price, Abu‐Ali, &
Huttenhower, 2016) suggests that the GM may in fact be the most
allostatic system within the body. Microbial dysbiosis then could be
considered an extreme and prolonged shift away from what would
be considered a relatively healthy composition which loses its abil‐
ity to regulate change in various other host systems and functions.
It is perhaps this dysregulation that manifests itself in psychological
illness.
Figure 1 depicts the three overarching pathways (endocrinolog‐
ical, neuronal, and immunological) of bidirectional communication
between the brain and the gut, each of which is altered during a
state of microbial dysbiosis. Although it remains unconfirmed, it is
proposed that microbial dysbiosis can be detected via interoception
| 7 of 19
which ultimately leads to altered functioning of factors (e.g., inflam‐
mation) that mediate these pathways. These alterations are believed
to be an allostatic response to a deviation from a “typical” microbi‐
ome, which over time, leads to symptom expression as a result of
allostatic overload. The bidirectional relationship between microbial
dysbiosis and the factors which alter the three main communication
pathways between the gut and the brain illustrate the multidirec‐
tional nature of the BGMA.
2 | G M TH RO U G H TH E LE N S O F A C A S E
FO R M U L ATI O N FR A M E WO R K
It is not the intention of this paper to propose that the BGMA must be
at the forefront of consideration for each and every client. Instead, it
is proposed that the relevance of the BGMA is determined on a case‐
by‐case basis. The role of the BGMA in a client's presenting prob‐
lem may be less relevant when there are clear social and emotional
etiological factors, such as the presence of significant stressors for
a client presenting with anxiety or depression. However, it is worth
noting that stress can alter the composition of a person's GM (Bailey
et al., 2011), which may or may not be clinically relevant, but should
be considered if comorbidities are present. It may also be less rel‐
evant for clients who respond well to traditional psychological treat‐
ments such as cognitive behavioral therapy. Alternatively, cases in
which the role or the BGMA may be more pertinent are when social
and emotional etiological factors are less clear or absent, and also
for clients who do not respond well to conventional psychological
approaches. In cases where a treating clinician considers investiga‐
tion of the GM to be appropriate, clients should be referred for stool
sampling and analysis and an open dialogue established between the
clinician and the microbiologist performing the analysis. The follow‐
ing information serves to highlight possible associations between
GM and each of the Four Ps.
2.1 | Predisposing
As part of their first line of questioning, mental health professionals
attempt to explore a client's family history of psychological illness
to establish whether that individual has an underlying genetic pre‐
disposition (vulnerability) to developing a psychological condition(s).
Genetic predisposition to a multitude of psychological conditions has
been well established (Hyman, 2000). While research into the role
of GM in genetic predisposition is scarce, several lines of evidence
suggest that GM may play an integral part in a person's vulnerability
to the development of psychological illnesses. Firstly, host genetics
have been demonstrated to influence the composition and meta‐
bolic activities of GM (Goodrich et al., 2014; Ussar, Fujisaka, & Kahn,
2016) which have important consequences on host physiology, brain
development, and health (e.g., Krishnan, Alden, & Lee, 2015; Sekirov,
Russell, Antunes, & Finlay, 2010). However, the specific mechanisms
behind this relationship remain unclear (Dąbrowska & Witkiewicz,
2016).
8 of 19 | GANCI et al.
2.1.1 | Vertical transmission
Additionally, there is evidence to suggest that much like genetics are
passed down from parents to offspring, GM are vertically transmit‐
ted from mother to infant (e.g., Asnicar et al., 2017; Mueller, Bakacs,
Combellick, Grigoryan, & Dominguez‐Bello, 2015). The transmis‐
sion of microbiota from mother to infant during birth represents
the most important point of microbial colonization in the infant gut,
which continues over the first three years of life (Yatsunenko et al.,
2012). This critical establishment period of GM is in line with the
critical development period of the human host (Rea et al., 2016).
It is during this time that GM play key roles in the development of
the CNS, HPA axis, and immune system (Borre et al., 2014; Cox et
al., 2014; Furusawa et al., 2013; Houghteling & Walker, 2015). As
such, aberrations in typical colonization of GM during this critical pe‐
riod may also result in abnormal development of these key systems
(Tamburini, Shen, Wu, & Clemente, 2016). Factors resulting in aber‐
rations to conventional microbial colonization of the gut during this
period, such as birth by cesarean section and antibiotic treatment
during infancy, have been associated with increased rates of chronic
and atopic diseases (Kolokotroni et al., 2012; Sevelsted, Stokholm,
Bonnelykke, & Bisgaard, 2015; Vangay, Ward, Gerber, & Knights,
2015). A recent study by Polidano, Zhu, and Bornstein (2017) high‐
lights the microbiota as a potentially important factor in the negative
relationship they found between cesarean birth and a range of cog‐
nitive outcomes compared to those born vaginally.
There is a growing consensus that maternal GM may have long‐
term health consequences for the child (Stanislawski et al., 2017).
It is therefore reasonable to suggest that vertically transmitted GM
may act as a mechanism for intergenerational predisposition to psy‐
chological disorders. Further research is required as it is difficult to
determine whether these intergenerational patterns are due to the
vertical transmission of GM or whether they are due to learned be‐
haviors and lifestyle factors shared among family members. This is
evidenced by same‐household members showing a higher similarity
of GM composition to those outside of the household (Abeles et al.,
2016; Song et al., 2013; Yatsunenko et al., 2012).
2.1.2 | Aging
Aging, in and of itself, can also predispose an individual to several
psychological illnesses. For example, neurodegenerative illnesses,
such as Alzheimer's disease, are considered an evolutionary acci‐
dent occurring as a result of increased longevity (Giunta et al., 2008;
Gluckman et al., 2011; Niccoli & Partridge, 2012). There is evidence
to suggest that psychological disorders are also more prevalent in
the elderly (e.g., Andreas et al., 2017). A contributing factor toward
the increased prevalence of disease in the elderly is that the nor‐
mal aging process is associated with compositional changes and re‐
duced diversity of GM (Biagi et al., 2010). In parallel, normal aging
is characterized by chronic low‐grade inflammation, a phenomenon
commonly referred to as “inflammaging” (Franceschi et al., 2007). It
is believed that this inflammation is, at least in part, attributable to
alterations in GM (Buford, 2017). Additionally, aging is associated
with changes in the serotonergic system which is also believed to
contribute to increased prevalence of psychological disorders in the
elderly (O'Mahony et al., 2015). The serotonergic system is regulated
by GM (Table 1), therefore making it vulnerable to compositional and
metabolic changes (O'Mahony et al., 2015; Rogers et al., 2016).
Given the sheer complexity of the systemic functioning of the
human body, there are likely to be several other processes through
which GM may be involved in predisposing individuals to the de‐
velopment of psychological illnesses. Further research into how GM
influence predisposition to psychological illness will be useful in in‐
forming preventative strategies to circumvent the growing burden
of such conditions. However, GM not only play a role in predisposing
an individual to certain psychological illnesses as highlighted above,
but also in the onset and maintenance of those negative health
outcomes.
2.2 | Precipitating and perpetuating
While psychologists tend to focus heavily on social and environ‐
mental factors involved in the onset and maintenance of psycho‐
logical disorders, biological factors, such as GM composition, also
contribute to these stages of disease. The maintenance of a diverse
microbial ecosystem in the gut is essential for optimal host func‐
tion (Moloney et al., 2014; Sekirov et al., 2010). On the other hand,
reduced diversity and microbial dysbiosis have been implicated in
various psychological, neurological, metabolic, functional gastroin‐
testinal disorders, and autoimmune disease states (Blumstein, Levy,
Mayer, & Harte, 2014). These include, but are not limited to, IBS
(Jeffery et al., 2012; Tana et al., 2010), autism (Finegold et al., 2002),
schizophrenia (Castro‐Nallar et al., 2015), myalgic encephalomyeli‐
tis/chronic fatigue syndrome (ME/CFS; Fremont, Coomans, Massart,
& Meirleir, 2013; Wallis, Butt, Ball, Lewis, & Bruck, 2016), multiple
sclerosis (Jangi et al., 2016), dementia (Alkasir, Li, Li, Jin, & Zhu,
2017), stress (Knowles, Nelson, & Palombo, 2008), anxiety (Burch,
2016), depression (e.g., Jiang et al., 2015), obesity (Ley, Turnbaugh,
Klein, & Gordon, 2006), diabetes (Larsen et al., 2010), coronary ar‐
tery disease (Cui, Zhao, Hu, Zhang, & Hua, 2017; Emoto et al., 2017),
and cancer (particularly colorectal cancer; Gagniere et al., 2016;
Garrett, 2015). Current findings linking GM and disorders are, at
this stage, associative and causative links are yet to be established.
Additionally, it is unknown whether alterations in GM composition
are the cause or consequence of disease. Given available evidence
however, it is likely that this is a bidirectional, and cyclical, relation‐
ship as depicted in Figure 1.
2.2.1 | Stress
Stress has long been recognized as both a precipitating and per‐
petuating factor to various psychological conditions (Anisman &
Zacharko, 1982; Corcoran et al., 2003). Given the crucial role of GM
in the development and functioning of the HPA axis (Sudo, 2012),
as well as their modulation of stress hormones CRF and cortisol
GANCI et al.
(Carabotti et al., 2015), the involvement of GM in the stress response
is increasingly evident. This is further demonstrated by the ability
to transfer stress‐prone phenotypes from one mouse to another via
fecal transplantation (Collins, Kassam, & Bercik, 2013). Stress also
activates an inflammatory response via the promotion of inflamma‐
tory cytokines (Liu, Wang, & Jiang, 2017). Given that inflammation
is recognized as underlying many psychological and neurodegen‐
erative disorders (Almond, 2013; Miller & Raison, 2016; Rea et al.,
2016), stress then appears to play a role in both the etiology and
maintenance of psychological illness via biological pathways, all of
which are regulated by the GM. While this is reflective of a bot‐
tom‐up process whereby GM influence stress, substantial evidence
also suggests the occurrence of a top‐down process through which
stress regulates GM composition (Bailey et al., 2011; Gur, Worly, &
Bailey, 2015; Knowles et al., 2008). The fact that both top‐down
and bottom‐up processes have been well established demonstrates
the complex cyclical and multidirectional relationship between GM,
stress, and psychopathology.
2.2.2 | Socioeconomic status
There is an established association between low SES and several fac‐
tors negatively affecting health, one of which is poor diet (Darmon
& Drewnowski, 2008; Shahar, Shai, Vardi, Shahar, & Fraser, 2005).
Given that diet is the strongest environmental contributor to a prop‐
erly functioning GM (e.g., De Filippo et al., 2017; Garcia‐Mantrana
et al., 2018), it is possible that the composition and/or metabolic
activities of the GM is one of the mediating factors of the relation‐
ship between low SES and mental health outcomes. Another fac‐
tor associated with low SES is lower educational achievement (Sirin,
2005) which may also be mediated by diet‐related changes in GM.
Individuals who eat a poor‐quality diet (Western diet) have poorer
performance on cognitive tasks (Khan et al., 2015) and poorer mental
health (Jacka, Kremer, et al., 2011; Jacka, Mykletun, Berk, Bjelland,
& Tell, 2011; Markus et al., 1998) compared to those who eat high‐
quality diets. In addition, an association has been found between the
consumption of a Western diet and decreased left hippocampal vol‐
ume (Jacka, Cherbuin, Anstey, Sachdev, & Butterworth, 2015) with
hippocampal volume being related to cognition (Choi et al., 2016)
and mood (Frodl et al., 2006). It is likely the GM mediate this rela‐
tionship through their production of SCFAs and BDNF which have
been found to be involved in neurogenesis and neuronal protection
in mouse models (Canani, Di Costanzo, & Leone, 2012; Lee, Duan, &
Mattson, 2002; Sun et al., 2015). Ultimately, poorer performance on
cognitive tasks and poorer mental health limit a person's educational
attainment (Eisenberg, Golberstein, & Hunt Justin, 2009; Fletcher,
2010; McLeod & Fettes, 2007).
2.3 | Protective
Considering the protective abilities of GM or indeed, specific mi‐
croorganisms, has the potential to revolutionize the treatment of
| 9 of 19
psychological conditions (Kali, 2016; Mazzoli & Pessione, 2016;
Sampson & Mazmanian, 2015). The addition of GM modulation to an
individual's treatment plan may be the missing link in explaining and
counteracting the alarming increase in the disease burden of com‐
mon mental disorders.
2.3.1 | Lifestyle factors
Healthy eating and exercise have long been promoted as being
protective factors against both physiological and psychological
conditions. Evidence suggests that one of the physiological mech‐
anisms through which healthy eating and exercise affect health is
the influence these factors have on the composition and metabolic
activity of GM (Mika et al., 2015; Welly et al., 2016). Essentially, a
high‐quality diet and exercise provide the GM with the resources
they require to maintain optimal host function. While the influ‐
ence of diet on GM composition is widely researched, that of ex‐
ercise on GM receives less attention. However, exercise has been
shown to enrich microbial diversity, improve the Bacteroidetes‐to‐
Firmicutes ratio, and support the growth of SCFA‐producing bac‐
teria which have immunomodulatory effects (Monda et al., 2017).
This suggests that like diet, the beneficial outcomes of exercise
may be mediated by GM which have downstream effects on men‐
tal health.
2.3.2 | Pre‐ and probiotics
Both pre‐ and probiotics have also been demonstrated to have psy‐
chotropic like effects in healthy volunteers as well as those suffering
from conditions such as depression and chronic fatigue syndrome
(CFS; Akkasheh et al., 2016; Messaoudi et al., 2011; Rao et al., 2009).
Probiotics showing positive effects on mental health are referred
to as psychobiotics (Dinan, Stanton, & Cryan, 2013). Studies have
demonstrated that various probiotic formulations (mostly including
Lactobacillus and Bifidobacterium species) have the ability to improve
mood in healthy (no reported diagnoses of allergic, neurological,
or psychological conditions) men and women (Benton, Williams, &
Brown, 2007; Messaoudi et al., 2011; Steenbergen, Sellaro, Hemert,
Bosch, & Colzato, 2015). In a placebo‐controlled study, Yamamura
et al. (2009) found a probiotic formulation to improve sleep efficacy
and number of awakenings (as measured by actigraphy) in an elderly
(60‐ to 81‐year‐old) sample. Moreover, a study using fMRI revealed
altered activity in brain regions responsible for emotion and sensa‐
tion processing in women following four weeks of probiotic formula‐
tion intake compared to women who received a placebo (Tillisch et
al., 2013). Also in a placebo‐controlled study, participants who took
a prebiotic (Bimuno‐galactooligosaccharides) daily for three weeks
showed significantly lower salivary cortisol levels and decreased at‐
tentional vigilance to negative versus positive information (Schmidt
et al., 2015). These findings were similar to those of a study that in‐
volved the administration of an SSRI (Murphy, Yiend, Lester, Cowen,
& Harmer, 2009).
10 of 19 | GANCI et al.
2.3.3 | Fecal microbial transplant
The increasing popularity of fecal microbial transplant (FMT) in
treating various conditions including but not limited to GI disorders
(Brandt & Aroniadis, 2013), Parkinson's disease (Ananthaswamy,
2011), autism (Aroniadis & Brandt, 2013), and ME/CFS (Borody,
Nowak, & Finlayson, 2012) is perhaps due to the proliferation of
research associating microbial dysbiosis to a range of disorders. In
humans, the efficacy of FMT has been shown for conditions such
as ulcerative colitis (Shi et al., 2016), but has not yet been demon‐
strated in treating psychological conditions. It does however offer
a promising avenue given strong evidence suggesting a role of GM
in the pathogenesis of psychological conditions (Evrensel & Ceylan,
2016). Animal models suggest that FMT is an effective way to ame‐
liorate abnormal physiology and function (e.g., Sudo et al., 2004);
however, clinical trials are required to demonstrate whether this ap‐
proach is equally effective in humans. Additionally, further research
is required into the possible risks associated with FMT. While FMT
has promising therapeutic potential, Alang and Kelly (2015) present
a case study of a patient who developed obesity following FMT
treatment from an overweight, but otherwise healthy donor. As GM
are associated with numerous physiological and psychological condi‐
tions, FMT could theoretically result in the transference of any such
condition from donor to recipient (Bunnik, Aarts, & Chen, 2017). As
such, it is clear that great care must be taken when screening and
selecting potential donors. There is still much to learn about the as‐
sociations between GM and both physiological and psychological
conditions, and therefore, potential long‐term risks of FMT may yet
to emerge.
3 | C R ITI C I S M S O F CO N V E NTI O N A L
TR E ATM E NT W ITH R E S PEC T TO G M
Conventional treatment of psychological disorders typically in‐
volves pharmacological intervention such as psychotropics and/or
other medications to alter brain chemistry (e.g., Bystritsky, Khalsa,
Cameron, & Schiffman, 2013; Lieberman et al., 2005). Although ben‐
eficial, such treatments may induce undesirable side effects includ‐
ing, but not limited to, nausea, sleep disturbance, weight gain, and
sexual dysfunction (Ferguson, 2001) all of which may themselves
be a result of microbe‐mediated drug metabolism (Enright, Joyce,
Gahan, & Griffin, 2017). Despite the ever increasing reliance on phar‐
macotherapy (Kallivayalil, 2008; Vozeh, 2003), disease states remain
relatively stable which suggests the need for auxiliary treatment op‐
tions and/or targets which take into account several body systems,
including the GM. Many psychotropic drugs, known for their influ‐
ence on CNS receptor function, also demonstrate antimicrobial ef‐
fects (Kalayci, Demirci, & Sahin, 2014) which may have unintended
consequences on the BGMA. This is particularly true of many SSRIs
commonly used to treat depression and anxiety disorders.
In addition to having direct antimicrobial effects, Ayaz et al.
(2015) found that sertraline (an SSRI) augments the effectiveness
of several antibiotics by increasing their inhibitory zone. As such,
chronic use of these drugs can induce potentially deleterious alter‐
ations in GM (Macedo et al., 2017). This may partially explain treat‐
ment resistance, although further research is needed to support this
notion. Likewise, psychological interventions (e.g., cognitive behav‐
ior therapy) also target the brain via a focus on cognitions to affect
behavioral change. This top‐down process has demonstrated effi‐
cacy in the treatment of functional gastrointestinal disorders such
as IBS (Boersma et al., 2016; Palsson & Whitehead, 2013); however,
research is needed to determine whether purely psychological in‐
terventions can enact changes in GM. By continuing to treat vari‐
ous disorders and symptoms through pharmacological intervention
without considering the etiology of initial chemical imbalances, it is
unlikely that rates of morbidity will decline. The net effect of ignor‐
ing etiology at the expense of treatment is therefore an increased
burden upon individuals who are affected by disease, and wider
society.
4 | R E D E FI N I N G W H O W E A R E
There is currently a shift away from thinking of host–microbe interac‐
tions in such binary terms toward appreciating the complexity of the
relationship between the two. Binary distinctions between host and
microbiota remain useful only in so far as to aid our understanding of
the role of GM in psychological well‐being, which is still in its infancy.
However, emerging nomenclature such as “holobiont” acknowledges
that GM are not a separate entity but are instead an integral and in‐
separable part of human biology (Schnorr, Sankaranarayanan, Lewis,
& Warinner, 2016; Theis et al., 2016). This concept is supported by
the coevolution of humans and their microbes. The concept that the
ratio of bacterial cells to human cells is approximately 1:1 (recently
revised down from previous estimations of 10:1; Sender, Fuchs, &
Milo, 2016) pays homage to the importance of respecting GM in the
conceptualization of human health and well‐being. This reconcep‐
tualization of what makes us human also provides a biological and
tangible basis for explaining and treating psychological illnesses that
can often be considered abstract.
5 | C H A LLE N G E S A N D TH E WAY
FO RWA R D
Understanding the multidirectional relationship between GM and
the nervous system is hindered by its inherent complexity (Mazzoli
& Pessione, 2016). However, while still in its infancy, interdiscipli‐
nary research has uncovered novel ways of conceptualizing disease.
While theoretically relevant, research into the BGMA also has im‐
portant practical implications, offering a more holistic approach to
treatment and prevention of psychological illness. While this new
field of research is promising, it remains unclear which factors, and
in which combination, alter the balance between symptomatic and
asymptomatic outcomes.
GANCI et al.
The sheer number of confounding variables makes it difficult
to establish causational links between GM and symptomatology.
However, as understanding of the GM advances, so too will research
methodology and technology. It is only with continued research into
the link between GM and psychological illness that we will be able to
elucidate the true extent to which our resident microbes contribute
to mental health. As the majority of studies regarding the role of
GM in both physiological and psychological health and disease have
been conducted using animal models, clinical trials with human sam‐
ples are imperative to the advancement of knowledge and ultimately
practical application.
As the burgeoning research into the relationship between GM
and psychological health outcomes gathers momentum, so too
does the call to action for psychologists to embrace the microbi‐
ome as a potential factor in explaining, treating, and preventing
mental illness. This is an important paradigm shift which must
occur within the discipline of psychology in order to keep up to
date with the most current and complete knowledge of the human
body and mind which translates into providing the best possible
care for clients. While it is unnecessary and impractical to expect
psychologists to develop a detailed understanding of the influence
of GM on mental health, it is important that the role of the GM is
acknowledged, especially in the absence of clear social and emo‐
tional factors. Facilitating this paradigm shift may require change
at a “grass roots” level, where psychobiology is better integrated
into higher education psychology degrees. Additionally, profes‐
sional development courses regarding the role of the GM in mental
health should be established and promoted to current practicing
psychologists who can use this information to provide more com‐
plete care for their clients.
The fact that GM are able to influence psychological functioning
is an exciting and encouraging prospect, which begs for multidisci‐
plinary approaches to both research and practice. In terms of prac‐
tical implications, increasing our understanding of the mechanisms
that mediate communication processes between GM and host has
the potential to inform strategies to limit the damaging aspects of
this communication. This will provide new avenues of treatment for a
wide range of symptoms and disorders (Freestone, 2013) as well as to
promote good health. This will require a substantial shift away from
the reductionist approaches that see us working exclusively in our
specific field. This is not to suggest that psychologists should become
expert in areas outside of their field, but instead to understand and ac‐
knowledge that the best way forward is a multidisciplinary approach
to the treatment and prevention of mental illness. A shift toward a
multidisciplinary, and therefore more holistic, approach will provide
an opportunity to better understand the etiology of disease which
requires the expertise of several disciplines and a consideration of
key body systems, including the GM, as intertwined and inseparable.
In light of the evidence research has provided thus far, psychologists
working as part of multidisciplinary teams with other professionals
such as nutritionists, gastroenterologists, and microbiologists must
seriously consider the inclusion of dietary plans, pre‐ and probiotics,
| 11 of 19
and potentially even FMT in the treatment plans of their clients, in
conjunction with conventional psychological treatments.
It is not the contention of this paper to claim that ameliorating
gut health is the panacea to all psychological disorders and symp‐
tomatology. Instead, it is to demonstrate the complex intercon‐
nectivity between multiple body systems in disease processes,
from etiology through to treatment, and ideally prevention. In
support of the call to action by Allen et al. (2017), the discipline of
psychology must shift away from its CNS‐centric conceptualiza‐
tion of disease and symptom‐centered disease treatment models
toward a multidisciplinary approach to treatment and prevention.
This paradigm shift will empower psychologists to better treat and
care for their clients. A multidisciplinary approach where health‐
care professionals across a variety of disciplines have a united ap‐
proach to treatment and prevention will also empower the public
to better understand and take control of their physiological and
psychological health. It is only through this shared awareness that
the healthcare community can make inroads into improving the
mental health of current and future generations.
C O N FL I C T O F I N T E R E S T
None declared.
DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were cre‐
ated or analyzed in this study.
ORCID
Michael Ganci https://orcid.org/0000-0003-2815-0548
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How to cite this article: Ganci M, Suleyman E, Butt H, Ball M.
The role of the brain–gut–microbiota axis in psychology: The
importance of considering gut microbiota in the development,
perpetuation, and treatment of psychological disorders. Brain
Behav. 2019;9:e01408. https​://doi.org/10.1002/brb3.1408